Evaluation of the Diagnostic Efficacy of a αvβ6/FAP-Targeting Heterodimeric Probe in Patients With Malignant Solid Tumors

This investigator-initiated trial (IIT) aims to evaluate the clinical utility of positron emission tomography (PET) imaging targeting both integrin αvβ6 and fibroblast activation protein (FAP) in patients with malignant solid tumors. Based on promising preclinical studies, we have designed and synthesized a bispecific probe, B6FA-01, which can simultaneously bind to both targets. By concurrently targeting two independent, highly expressed targets-one on tumor epithelial cells (αvβ6) and one within the tumor stroma (FAP)-this probe is expected to address the issue of receptor heterogeneity that limits current single-target probes like ⁶⁸Ga-FAPI or ⁶⁸Ga-Trivehexin. Indeed, preclinical data indicate that ⁶⁸Ga-B6FA-01 exhibits not only excellent targeting affinity and specificity but also higher tumor uptake, longer intratumoral retention, faster renal clearance, and a favorable biocompatibility profile compared to its single-target counterparts.

In this prospective study, patients with histologically confirmed malignant solid tumors will undergo ⁶⁸Ga-B6FA-01 PET/CT imaging. Key PET parameters-including the maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), and tumor-to-background ratio (TBR)-will be analyzed to assess their diagnostic performance (sensitivity, specificity, accuracy). Furthermore, the study will explore the correlation between these in vivo imaging parameters and the ex vivo expression levels of αvβ6 and FAP in tumor tissues.

The findings from this study could establish αvβ6- and FAP-targeted PET imaging as a superior, non-invasive tool for tumor diagnosis and treatment assessment.

Inclusion criteria

• Voluntarily provide written informed consent.
• Age ≥ 18 years.
• Newly diagnosed with a clinically/radiologically suspected or pathologically confirmed malignant solid tumor, or with suspected recurrence after prior treatment.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1.
• Life expectancy > 6 months.
• Participants of childbearing potential and their partners must agree to use highly effective contraception for 6 months following the last dose of the investigational agent.

Exclusion criteria

• Prior radioisotope therapy within an interval less than 10 times the physical half-life of the respective radionuclide before study administration.
• Concurrent participation in any other interventional clinical trial.
• Known allergy or hypersensitivity to the investigational agent or any of its excipients.
• Inability to lie still for the duration of the PET scan or any condition contraindicating PET imaging.
• Pregnancy or lactation.
• Any other condition that, in the investigator's judgment, would compromise participant safety or study integrity.